Conclusions drawn from our recent work demonstrate that the central problem in gallstone pathogenesis is no longer merely the presence of cholesterol in amounts exceeding maximum solubility. The present work based on this is directed towards providing at least partial answers to two important questions: First, What causes cholesterol to precipitate from some supersaturated (abnormal) biles and not from others (normal)? and second, What can enhance the rate of dissolution of precipitated cholesterol (gallstones)? Specific observations will be obtained on the following: 1. Rates of cholesterol nucleation and precipitation from supersaturated in vitro solutions patterned after bile. a) Effects of liquid crystalline mesophases on the rate of nucleation and precipitation. b) Effects of various isolated non-lipid biliary constituents on rates of nucleation and precipitation. 2. Rates of cholesterol dissolution into undersaturated in vitro solutions patterned after bile. Effects of same factors as above will be studied. 3. Physiological relevance of rate controlling factors, identified by in vitro model solution studies, in natural bile. 4. Effect of dilution on maximum cholesterol solubility of in vitro model solutions and natural bile. Methods used in measuring rates of precipitate formation will include: Use of C14 cholesterol labelling, particle counting techniques and serial polarizing microscopy. In addition, a direct chemical characterization of the lipid crystalline mesophase in bile and its effect on nucleation and dissolution will be accomplished to determine its role in the system.